Rational modulator design by exploitation of protein-protein complex structures

Kanin Wichapong, Hessel Poelman, Bogac Ercig, Johana Hrdinova, Xiaosong Liu, Esther Lutgens, Gerry A.F. Nicolaes

Research output: Contribution to journalReview articlepeer-review


The horizon of drug discovery is currently expanding to target and modulate protein-protein interactions (PPIs) in globular proteins and intrinsically disordered proteins that are involved in various diseases. To either interrupt or stabilize PPIs, the 3D structure of target protein-protein (or protein-peptide) complexes can be exploited to rationally design PPI modulators (inhibitors or stabilizers) through structure-based molecular design. In this review, we present an overview of experimental and computational methods that can be used to determine 3D structures of protein-protein complexes. Several approaches including rational and in silico methods that can be applied to design peptides, peptidomimetics and small compounds by utilization of determined 3D protein-protein/peptide complexes are summarized and illustrated.

Original languageEnglish (US)
Pages (from-to)1015-1033
Number of pages19
JournalFuture Medicinal Chemistry
Issue number9
StatePublished - 2019


  • PPI modulators
  • intrinsically disordered proteins
  • peptide design
  • peptidomimetics
  • protein-protein interactions

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery


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